Bulletin of the Transilvania University of Braşov Series VI: Medical Sciences Vol. 7 (56) No. 1-2014 ETHIOLOGICAL AND THERAPEUTICAL PARTICULARITIES OF URINARY INFECTIONS IN UROLOGICAL PATIENTS G.G. MATEESCU 1 M.E. IDOMIR 1 C. NEMET 1 Abstract: The aim of our retrospective study was to analyze in dynamics the etiological spectrum of the urinary infections in patients hospitalized in the Urology ward of the Clinical County Emergency Hospital Braşov during 2011-2013. The levels of the antimicrobial resistance of the implicated germs was also evaluated. The main involved agent in both studied years was E. coli, followed by other Enterobacteriaceae (Klebsiella spp., Enterobacter spp., Proteus spp., Serratia spp., Citrobacter spp.), Enterococcus spp., Staphylococcus spp. and non-fermentative bacilli (Pseudomonas aeruginosa, Acinetobacter spp.). There were registered different levels of resistance to the tested antibiotics. We have observed an increase of the shares of Extended spectrum beta-lactamase producing strains and of the High - Level Aminoglycoside Resistance strains. Key words: urinary infections, antimicrobial resistance, ESBLs. 1. Introduction In present it is considered that urinary tract infections are situated on the second place as frequency among acute human infections, after the upper respiratory tract infections. [5] This pathology is extremely common in woman who, due to the anatomical reasons (shorter urethra), the sexual intercourses and the use of de contraceptive means, have a high risk to develop infections (lifetime risk greater than %) with recurrent episodes (20% of woman with a first urinary infection) [4], [5], [9], [11], [13], [18]. In men, urinary infections are not as frequent but in the absence of appropiate therapy can lead to life threatening events generated through septicemia, to acute local complications or to evolution with recurrent episodes [5], [18]. The risk factors of urinary tract infections can be genetic predispositions, obstructions of urinary tract (stones, tumors, strictures, tumor of prostate), neurological disorders (Parkinson's disease, spinal cord injuries, multiple sclerosis, peripheral nerve damage), immune-supressions, debilitating diseases (diabetes mellitus), urological (catheters, tubes) or contraceptive devices (spermicidal agents and diaphragms), deficitary personal hygiene, pregnancy, menopause etc [2], [3], [4], [5], [8], [], [17], [18]. Several studies indicate Escherichia coli as being the main agent of urinary infections, implicated in 70-95% of urinary infections. 1 Faculty of Medicine, Transilvania University of Braşov.
20 Bulletin of the Transilvania University of Braşov Series VI Vol. 7 (56) No. 1-2014 The second uropathogenic species is considered to be Klebsiella pneumoniae. There were also reported other Enterobacteriaceae (Proteus, Enterobacter, Serratia, Citrobacter, Morganella, Salmonella) as having significant frequences followed by Enterococcus spp., Staphylococcus, Pseudomonas aeruginosa, Acinetobacter species [2], [3], [4], [5], [9], [11], [12], [15]. Urinary infections represent up to 40% of all the hospital-acquired infections. The antibiotherapy of hospital-acquired infections raise therapeutical problems due to the resistance to antibiotics, mainly for the ESBL (Extended Spectrum Beta-lactamase) and HLAR (High Level Aminoglycoside Resistance) strains [1], [6], [8], [14], [16]. 2. Material and methods The aim of our retrospective, descriptive study was to analyze the particularities of urinary tract infections in urological patients. For this purpose, there has been analyzed the etiological spectrum of these infections as well as the levels and resistance patterns to antibiotics of the implicated germs. There have been analysed 426 bacterial strains isolated through urine culture from the patients hospitalized in the Urology ward of the Clinical Emergency County Hospital of Braşov. In order to determine the dynamics of isolated urinary pathogens implicated in the urinary infections in urological patients, the study has included two periods of 6 months (1.01.2011-30.06.2011; 1.01.2013-30.06.2013). For the identification of the gram negative germs, have been used biochemical tests (Triple Sugar Iron Agar, Urea Agar, S.I.M. Medium, Simmons Citrate Agar and Oxidase test). For Enterococcus strains, was performed the bile-esculin test. The coagulase test, AVIPATH STAPH latex agglutination, pigmentogenesis, beta - hemolisis, were taken into consideration for the Staphylococcus strains. Antibiogram was performed according to the C.L.S.I. (Clinical Laboratory Standard Institute). The sinergy test was used for the detection of the E.S.B.L. (Extended Spectrum Beta Lactamases) strains. 3. Results and discussions We have initially analyzed the dynamics of the bacterial strains isolated from urine in patients hospitalized in the Urology ward of the County Clinical Emergency Hospital of Brasov during 6 months periods in 2011 and 2013. The dynamics of the number of gram negative bacilli implicated in urinary tract infections is presented in Figure 1. Nr. strains 90 80 70 60 40 30 20 0 86 24 16 15 6 2 1 78 13 5 3 0 Escherichia coli Klebsiella spp. Pseudomonas spp. Enterobacter spp. Proteus spp. Serratia spp. Citrobacter spp. Acinetobacter spp. Fig.1. The dynamics of the gram negative bacilli isolated from urine 58
G.G. MATEESCU et al.: Ethiological and Therapetical Particularities of Urinary Infections... 21 The dynamics of the number of gram positive cocci is shown in Figure 2. years, excepting Acinetobacter spp. which was isolated only in 2011. 60 40 51 Enterobacter spp. 5.5% Pseudomonas spp. 4.2% Staphylococcus Proteus spp. aureus 4.2% 0.4% Serratia spp. 1.3% Citrobacter spp. 2.1% Acinetobacter spp. 0.0% Nr. strains 30 20 22 Enterococcus spp. 21.6% Staphylococcus spp. 3.0% 0 5 3 Enterococcus spp. Staphylococcus aureus Staphylococcus spp. Fig. 2. The dynamics of gram positive cocci isolated from urine 7 1 Klebsiella spp. 24.6% Escherichia coli 33.1% Fig. 4. The etiological spectrum of urinary infections between January and June 2013 The etiological spectrum of the urinary tract infections in the year 2011 and 2013 are illustrated in the Figure nr 3 and Figure nr 4 respectively. Pseudomonas spp. 8.4% Enterococcus spp. 11.6% Proteus spp. 5.3% Enterobacter spp. 7.9% Staphylococcus aureus 2.6% Staphylococcus spp. 1.6% Serratia spp. 3.2% Citrobacter spp. 1.1% Acinetobacter spp. 0.5% % resistent strains 0.00 90.00 80.00 70.00 60.00.00 40.00 30.00 20.00.00 61.60 43.00 32.60 31.40 23.30 15. 70.70 53.80 46.20 25.60 24.00 23. 20. Klebsiella spp. 12.6% Escherichia coli 45.3% Fig. 3. The etiological spectrum of urinary infections between January and June 2011 The etiological spectrum of urinary tract infections was the same in both studied 0.00 Amp Amc Caz Cro Nor Na G Fig. 5. Antibiotic resistance in urinary isolates of E. coli
22 Bulletin of the Transilvania University of Braşov Series VI Vol. 7 (56) No. 1-2014 For the isolated bacterial strains, various antibiotics were tested through difusimetric antibiogram: beta-lactams (penicillin P; ampicillin Amp; amoxicillin clavulanic acid Amc; ceftriaxone Cro; ceftazidime Caz; imipenem Ipm), fluoroquinolones (nalidixic acid Na; Norfloxacin Nor; Levofloxacin - Lev), aminoglycosides (gentamicin G; amikacin - Ak), glycopeptides (vancomycin, teicoplanin) and other antimicrobials (colistin; chloramphenicol). The percentage of the resistant E. coli, Klebsiella and Enterococcus strains for each of the tested antibiotics is illustrated in Figures nr 5, number 6 and 7 respectivly. 0 90 0 0 % resistent strains 0.0 80.0 60.0 40.0 20.0 0.0 45.5 13.6 4.5 P Amp Lev Nor C 88.2 80.2 19.4 14.0 Fig. 7. Antibiotic resistance in urinary isolates of Enterococcus spp. There were also analyzed the multiresistant bacterial strains isolated from urine samples. The share of ESBLs was slightly higher in 2013 compared to 2011 as shown in the Figure 8. % resistent strains 80 70 60 73.7 72.4 70.7 69 66.7 67.2 66.7 58.3 54.2 40 30 20 29.2 Amp Amc Caz Cro Nor Na G Ak Fig. 6. Antibiotic resistance in urinary isolates of Klebsiella spp. 25 Fig. 8. Dynamics of ESBL strains The ESBL strains detected in 2011 were 16 Escherichia coli (55%), 7 Klebsiella spp. (24%) and 6 Enterobacter spp. (21%). We have also analyzed the share of HLAR Enterococcus strains for the studied years, as shown in Figure 9.
G.G. MATEESCU et al.: Ethiological and Therapetical Particularities of Urinary Infections... 23 strains in case of penicillin, ampicillin, chloramphenicol, levofloxacin, norfloxacin. The obtained results regarding the antimicrobial resistance are consistent with those of other published studies [1], [6], [7], [8], [14], [16]. 4. Conclusions Fig. 9. Dynamics of HLAR strains During the study, the number of isolated Staphylococcus species was low and the number of M.R.S.A. strains (Methicillin Resistant Staphylococcus aureus) was also small (2 strains in 2011 and 1 strains in 2013). The analysis in dynamics (period of 2011 compared to 2013) of the urinary tract infections spectrum in patients hospitalized in the Urology ward indicates that the main etiological agent was E. coli, folowed by Klebsiella pneumoniae and Enterococcus spp. The obtained results are similar with those of other studies that were carried out in the same medical units or published in the medical literature [2], [3], [4], [5], [7], [9], [11], [12], [15]. Although the etiologic spectrum was similar in the two years studied, the frequencies of Klebsiella and Enterococcus spp. strains have increased. As in other studies, for Enterobacteriaceae there were obtained different shares of resistant strains to the tested antibiotics excepting imipenem and colistin for which all Escherichia coli and Klebsiella strains were susceptible. All isolated Enterococcus species strains were sensitive to vancomycin, teicoplanin, linezolid but there were detected resistant The main etiological agent of the urinary tract infections in urological patient was E. coli, with lower frequencies being also isolated other Enterobacteriaceae, enterococci, staphylococci and non-fermentative gram negative bacilli (Pseudomonas aeruginosa, Acinetobacter spp.). The analysis in dynamics of the ethiological spectrum has included the same bacterial species but the number of Klebsiella strains and Enterococcus strains has increased. There was registred an increase of E. coli strains resistant to nalidixic acid, gerntamicin and ampicillin. For Klebsiella spp. there was observed an increase of the number of resistant strains to the tested antibiotics excepting to amikacin and norfloxacin. In case of Enterococcus spp. we have found an increasing number of strains resistant to quinolones. References 1. Adhikari, L.: High-level Aminoglycoside Resistance and Reduced Susceptibility to Vancomycin in Nosocomial Enterococci. In: Journal of Global Infections Disease 20, 2(3), p. 231 235. 2. Adukauskiene, D., Kinderyte, A., et al.: Etiology, risk factors and outcome of urinary tract infection. In: Medicina (Kaunas) 2006, vol. 42, p. 805 809. 3. Akter, S., Hossain, A., et al.: Etiology of urinary tract infection in obstretic patients attended an urban hospital in
24 Bulletin of the Transilvania University of Braşov Series VI Vol. 7 (56) No. 1-2014 Dhaka, Bangladesh. In: Annals of Biological Research 2014, 5(1), p. 1-8. 4. Behzadi, P., Behzadi, E.: The Microbial Agents of Urinary Tract Infections at Central Laboratory of Dr. Shariati Hospital, Tehran, IRAN. In: Turkiye Klinikleri Journal of Medical Sciences, (2008), vol. 28, p. 445 449. 5. Behzadi, P., Yazdanbod, H., et al.: A survey of urinary tract infections associated with the three most common uropathogenic bacteria. In: Maedica, 20, 5(2), p. 111-115. 6. Hadžić, S., Čustović, A., Smajlović, J., et al.: Distribution of nosocomial infections caused by Klebsiella pneumoniae ESBL strain. In: Journal of Environmental and Occupational Science Periodical of GESDAV Journal Home Page 2012, 1(3), p. 141-146. 7. Idomir, M., Gavrilă, G., Nemet, C., Chichernea, N., Manafu, E.: Infecţiile urinare cu enterobacteriaceae dificultăţi terapeutice (Urinary infections with enterobacteriaceaetherapeutic difficulties). In: Jurnal Medical Braşovean 20, nr. 3, p. 62-65. 8. Kalsi, J., Arya, M., et al.: Hospitalacquired urinary tract infection. In: International Journal of Clinical Practice 2003, 57(5), p. 388-391. 9. Kodner, C.M., Gupton, E.K.T.: Recurrent Urinary Tract Infections in Women: Diagnosis and Management. In: American Physician 20, 82(6), p. 638-643.. Moore, K.N., Day, R.A., Albers, M.: Pathogenesis of urinary tract infections: a review. In: Journal of Clinical Nursing 2002, vol. 11, p. 568 574. 11. Mwaka, A.D., Mayanja-Kizza, H., et al.: Bacteriuria among adult nonpregnant women attending Mulago hospital assessment centre in Uganda. In: African Health Sciences 2011, 11(2), p. 182-189. 12. Obiogbolu, C.H., Okonko, I.O., et al.: Incidence of Urinary Tract Infections (UTIs) among pregnant women in Akwa metropolis, Southeastern Nigeria. In: Scientific Research and Essays 2009, vol. 4, p. 820 824. 13. Hummers-Pradier, E., Kochen, M.M., et al - Urinary tract infections in adult general practice patients. In: The British Journal of General Practice 2002, 52(482), p. 752 761. 14. Saint, S., Kowalski, C.P., et al.: Preventing Hospital-Acquired Urinary Tract Infection in the United States: A National Study. In: Clinical Infections Diseases 2008, 46(2), p. 243-2. 15. Shirishkumar, P., Taviad, P.P., et al.: Urinary tract infections (UTI) among patients at G.G.Hospital & Medical College, Jamnagar. In: National Journal of Community Medicine 2012, vol. 3, issue 1, p. 138-141. 16. Taskaban, I.M., Durusoy, R., et al.: Hospital-acquired urinary tract infection point prevalence in Turkey: differences in risk factors among patient groups. In: Annals of Clinical Microbiology and Antimicrobials 2013, 4(12), p. 31. 17. http://emedicine.medscape.com/article/ 1958794-overview, accesed 12 May 2014. 18. http://kidney.niddk.nih.gov/kudiseases/p ubs/utiadult/#causes